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Additional file 1. The farina of Primula bullata var bullata comprises very short fibres. SEM microscope images of the leaf farina threads is shown in (A). Red arrows indicate short threads. Wool thread diameter mean value and range is shown in (B). Raman spectra comparisons between P. bullata, Dionysia tapetodes and Primula marginata are shown in (C). Arrows show peaks that are shared between samples.

Additional file 3. Confocal transmitted image (A, C) and cell wall fluorescence (B, D) of calcofluor-stained sections through gland hair cells. Wool exit holes, observed as discrete gaps in the fluorescence images (arrows) are in close proximity to the dense vacuole (V).

Additional file 2. All data and interpretations plus commentary for HLPC, LCMS, HRMS and NMR chemical analyses.

Additional file 6. FE-SEM large area tile-scan of a section thorough the rosette leaves of D. tapetodes. The high resolution tile images enable organelles to be resolved. Magnified examples of glandular head cells and nearby leaf mesophyll cells are shown. Red arrows identify candidate electron-transparent organelles that may be lipid droplets. Yellow arrows identify similar sized electron dense droplets. The full resolution tiled image of size 35,172 x 46,156 pixels is deposited at http://dx.doi.org/10.17632/tk534bkb85.1.

Additional file 5. FE-SEM images showing intact and continuous membranes from young trichomes and leaf cells. Note these images were taken from the same section as the farina producing glandular trichomes shown in Fig. 4j-n.

Additional file 4. Fluorescence Lifetime Imaging (FLIM) of glandular trichomes taken together with Raman spectra acquired along a line through a trichome cell. The FLIM data (centre left image) represents lifetimes of autofluorescence. Farinose material including the wool and edge of the trichome cell have short lifetimes (cyan and blue colours) with high signal and the cell interior has blue (short) and green (long) lifetimes with low signal. Raman measurements at precise locations along the line confirm the presence of flavone-type material at the cell edge together with strong peaks equivalent to those of plant epicuticular wax (Upper spectrum, assignments are given for prominent peaks). Note the intense cyan labelling in the FLIM image that is a similar lifetime to the woolly farina (white boxed region). Within a proximal location inside the cell there is an absence of the wax-associated peaks and the strong flavone peaks (lower spectrum). Carotenoid is detected at both locations. Another location inside the cell yielded strong flavone peaks (centre spectrum) and may represent an intracellular store of flavones.

Novel divergent methodology to access sp3-rich spirocyclic fragments is reported. First, a robust modular synthesis of bis-alkene amino ester building blocks was developed. Three different carbocycles and six heterocycles were then constructed to assemble eight spirocycles. Importantly, strategic exit vectors were incorporated within each scaffold to aid fragment growth and were elaborated via chemical modifications. Finally, computational methods demonstrate higher levels of rigidity, three-dimensionality, and structural diversity of the library compared to a commercial collection.

Analogs of the known inhibitor (peptide pDI) of the p53/MDM2 protein–protein interaction are reported, which are stapled by linkers bearing a photoisomerizable diarylethene moiety. The corresponding photoisomers possess significantly different affinities to the p53-interacting domain of the human MDM2. Apparent dissociation constants are in the picomolar-to-low nanomolar range for those isomers with diarylethene in the “open” configuration, but up to eight times larger for the corresponding “closed” isomers. Spectroscopic, structural, and computational studies showed that the stapling linkers of the peptides contribute to their binding. Calorimetry revealed that the binding of the “closed” isomers is mostly enthalpy-driven, whereas the “open” photoforms bind to the protein stronger due to their increased binding entropy. The results suggest that conformational dynamics of the protein-peptide complexes may explain the differences in the thermodynamic profiles of the binding.

Polo-like kinase 1 (PLK1) is a key regulator of mitosis and a recognized drug target for cancer therapy. Inhibiting the polo-box domain of PLK1 offers potential advantages of increased selectivity and subsequently reduced toxicity compared with targeting the kinase domain. However, many if not all existing polo-box domain inhibitors have been shown to be unsuitable for further development. In this paper, we describe a novel compound series, which inhibits the protein-protein interactions of PLK1 via the polo-box domain. We combine high throughput screening with molecular modeling and computer-aided design, synthetic chemistry, and cell biology to address some of the common problems with protein-protein interaction inhibitors, such as solubility and potency. We use molecular modeling to improve the solubility of a hit series with initially poor physicochemical properties, enabling biophysical and biochemical characterization. We isolate and characterize enantiomers to improve potency and demonstrate on-target activity in both cell-free and cell-based assays, entirely consistent with the proposed binding model. The resulting compound series represents a promising starting point for further progression along the drug discovery pipeline and a new tool compound to study kinase-independent PLK functions.